As the results of the studies by DeLuca and Kodicek on the separation and identification of the metabolites of vitamin D.sub.3 and on its metabolism, it has been established that vitamin D.sub.3 is first hydroxylated (at 25-position) in the liver to form 25-hydroxyvitamin D.sub.3, then is hydroxylated (at 24-position or at 1.alpha.-position) in the kidney to form 24,25-hydroxyvitamin D.sub.3, or 1.alpha.,25-dihydroxyvitamin D.sub.3 and 1.alpha.,24,25-trihydroxyvitamin D.sub.3. It is also well known that these metabolites and other synthetic analogs, such as 1.alpha.-hydroxyvitamin D.sub.3, thereof enhance intestinal calcium transport and bone mineral mobilization and are useful as therapeutic agents to treat the diseases caused by various disorders in calcium metabolism.
The present inventors administered Alfarol (the trademark for a 1.alpha.-hydroxyvitamin D.sub.3 preparation made by the Chugai Seiyaku Kabushiki Kaisha) to patients who were under hemodialysis because of chronic renal failure and suffered from fever and leukocytosis, resulting in following unexpected clinical status: the fever which could not be abated by antibiotics such as kanamycin and rifampicin or steroid hormones reduced to the normal level, the blast granulocytes attributable to myeloproliferative disorders disappeared, and the count of leukocytes became normal.
To understand the mechanism of 1.alpha.-hydroxyvitamin D.sub.3 in remarkably improving the systemic conditions of the treated patients, the present inventors have performed series of experiments with a myeloid leukemia cell line (Ml) isolated from an SL mouse with myeloid leukemia, finding that the 1.alpha.-hydroxyvitamin D.sub.3 is about 100 times as potent in the production of macrophage-inducing factor from Ml cells as dexamethasone the most potent inducer ever known. This observation was confirmed by the changes in the morphology of the Ml cells, their adhesion to the dish surface, an increase in the lysozyme activity, the induction of phagocytic activity, and the appearance of Fc and C3 receptors on the cell surface.